Answer these questions for bds 1st year pharmacology exam of Kathmandu University

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CVS Pharmacology - BDS 1st Year (Kathmandu University)

Q1. MOA, Uses, and Adverse Effects of Nitrates [3+1+1=5]

Mechanism of Action (MOA)

Organic nitrates (e.g., nitroglycerin/GTN, isosorbide dinitrate) are metabolized in vascular smooth muscle to release nitric oxide (NO). The key steps are:

Nitrate → NO (via mitochondrial aldehyde dehydrogenase, ALDH2, and other enzymes)
NO activates soluble guanylyl cyclase → ↑ cGMP
↑ cGMP activates protein kinase G → ↓ myosin light-chain phosphorylation → ↓ intracellular Ca²⁺ → smooth muscle relaxation and vasodilation

Hemodynamically: Low doses dilate veins (↓ preload), higher doses dilate arteries (↓ afterload). Net effect = ↓ O₂ demand, ↑ O₂ supply to myocardium.

Uses

Stable, unstable, and variant (Prinzmetal's) angina
Acute myocardial infarction
Congestive heart failure (as adjunct)
Hypertensive emergency (IV nitroglycerin/nitroprusside)

Adverse Effects

Headache (most common - due to meningeal vessel dilation)
Postural hypotension, dizziness, flushing
Reflex tachycardia
Tolerance (tachyphylaxis) with continuous use
Contraindicated with PDE-5 inhibitors (sildenafil) - severe hypotension risk

Q2. Classify Antihypertensive Drugs with One Example Each; MOA of Nitroglycerin; Two Indications and 4 Adverse Effects [3+3+3=9]

Classification of Antihypertensive Drugs

Class	Example
Diuretics	Hydrochlorothiazide
Beta-blockers (β-blockers)	Atenolol
Calcium Channel Blockers (CCBs)	Amlodipine
ACE Inhibitors	Enalapril/Captopril
Angiotensin Receptor Blockers (ARBs)	Losartan
Alpha-blockers (α₁-blockers)	Prazosin
Centrally acting agents	Clonidine, Methyldopa
Direct vasodilators	Hydralazine, Minoxidil

All act by: reducing cardiac output, reducing peripheral vascular resistance, or reducing blood volume.

MOA of Nitroglycerin (as an antihypertensive)

Nitroglycerin releases NO → activates guanylyl cyclase → ↑ cGMP → smooth muscle relaxation → vasodilation of both veins and arteries → ↓ preload and afterload → ↓ blood pressure.

Two Indications

Hypertensive emergency (IV formulation)
Angina pectoris (stable, unstable, variant)

4 Adverse Effects of Nitroglycerin

Throbbing headache
Postural hypotension and syncope
Reflex tachycardia
Drug tolerance (tachyphylaxis with continuous/long-term use)

Q2(b). MOA, Uses, and Adverse Effects of Captopril [1+1+1]

MOA

Captopril is an ACE (Angiotensin Converting Enzyme) Inhibitor with a sulfhydryl (-SH) group:

Angiotensinogen → (renin) → Angiotensin I → (ACE) → Angiotensin II

Captopril blocks ACE → ↓ Angiotensin II formation → ↓ vasoconstriction + ↓ aldosterone secretion → ↓ sodium/water retention → ↓ blood pressure.

Also inhibits breakdown of bradykinin (a vasodilator) - contributing to blood pressure lowering (and to the side effect of cough).

Uses

Hypertension
Heart failure (reduces mortality)
Post-MI (left ventricular dysfunction)
Diabetic nephropathy

Adverse Effects

Dry, persistent cough (most common - due to ↑ bradykinin)
Angioedema (potentially life-threatening)
Hyperkalemia
First-dose hypotension
Rash, dysgeusia (altered taste)
Teratogenic - contraindicated in pregnancy

Q3. List Antianginal Drugs; MOA and Adverse Effects of Nitrates [1+2+2=5]

List of Antianginal Drugs

Nitrates - Nitroglycerin, Isosorbide dinitrate (ISDN), Isosorbide mononitrate
Beta-blockers - Atenolol, Metoprolol
Calcium Channel Blockers - Amlodipine, Verapamil, Diltiazem
Potassium channel openers - Nicorandil
If-channel blocker - Ivabradine
Others - Ranolazine

MOA of Nitrates

(See Q1 above - NO → cGMP → smooth muscle relaxation → vasodilation → ↓ preload (venodilation) → ↓ myocardial O₂ demand)

Adverse Effects of Nitrates

Headache (very common)
Postural hypotension
Reflex tachycardia
Tolerance/tachyphylaxis (overcome with nitrate-free intervals)
Contraindicated with sildenafil (risk of severe hypotension)

Q4. Drugs in Management of Congestive Heart Failure (CHF); MOA of Digoxin [3+2=5]

Drugs Used in CHF (with examples)

Class	Example
Cardiac glycosides	Digoxin
ACE Inhibitors	Enalapril, Captopril
ARBs	Losartan
Beta-blockers	Carvedilol, Bisoprolol
Diuretics - Loop	Furosemide
Diuretics - Aldosterone antagonist	Spironolactone
Vasodilators	Hydralazine + Nitrates
Positive inotropes	Dobutamine (acute)
SGLT2 inhibitors	Dapagliflozin (newer)

MOA of Digoxin

Digoxin is a cardiac glycoside that acts by:

Inhibits Na⁺/K⁺-ATPase pump on cardiomyocyte membranes
→ ↑ intracellular Na⁺ → reduces Na⁺/Ca²⁺ exchange → ↑ intracellular Ca²⁺
→ ↑ myocardial contractility (positive inotropy) - useful in heart failure
Also acts via vagus nerve → ↓ heart rate (negative chronotropy) - useful in atrial fibrillation

Short Notes

a) Digitalis Toxicity

Cardiac: Bradycardia, AV block, ventricular tachycardia/fibrillation, bigeminy
GI: Nausea, vomiting, anorexia, diarrhea
CNS/Visual: Xanthopsia (yellow-green vision), confusion, fatigue
Precipitating factors: Hypokalemia, hypomagnesemia, renal failure, hypothyroidism
Treatment: Stop digoxin, correct electrolytes (K⁺), digoxin-specific antibody fragments (Digibind) for severe cases

b) Drugs in Myocardial Infarction (MI)

Acute management (MONAB):

Morphine - pain relief, reduces anxiety and preload
Oxygen - for hypoxia
Nitrates - pain relief, vasodilation
Aspirin + Clopidogrel - antiplatelet
Beta-blocker - reduces infarct size, mortality

Others:

Thrombolytics (Streptokinase, tPA) - if PCI unavailable
Heparin (anticoagulant)
ACE inhibitors - post-MI, reduces remodeling
Statins - plaque stabilization

c) MOA of Digoxin

(See Q4 above)

d) Dyslipidemic Drugs (Classification)

Class	Examples
Statins (HMG-CoA reductase inhibitors)	Atorvastatin, Rosuvastatin
Fibrates	Gemfibrozil, Fenofibrate
Bile acid sequestrants	Cholestyramine
Niacin (nicotinic acid)	Niacin
Cholesterol absorption inhibitors	Ezetimibe
PCSK9 inhibitors	Evolocumab
Omega-3 fatty acids	Fish oil

e) Calcium Channel Blockers (CCBs)

Classification:

Dihydropyridines (vascular selective): Amlodipine, Nifedipine - used in hypertension, angina
Non-dihydropyridines (cardiac + vascular): Verapamil (phenylalkylamine), Diltiazem (benzothiazepine) - used in arrhythmias, angina

MOA: Block L-type voltage-gated Ca²⁺ channels → ↓ Ca²⁺ entry into vascular smooth muscle (vasodilation) and cardiomyocytes (↓ HR, ↓ contractility for non-DHPs)

Adverse effects: Flushing, edema, constipation (verapamil), bradycardia

f) ACE Inhibitors

(See Captopril above - same class)

Q6. Classify Anti-Hyperlipidemic Drugs; Brief Account of Statins [3+3]

Classification

(See dyslipidemic drugs table above)

Statins - Brief Account

Drug examples: Atorvastatin, Simvastatin, Rosuvastatin, Pravastatin

MOA: Inhibit HMG-CoA reductase (rate-limiting enzyme in cholesterol synthesis in the liver) → ↓ hepatic cholesterol → upregulation of LDL receptors → ↑ LDL clearance from blood

Effects: ↓ LDL (most potent effect), ↓ TG, mild ↑ HDL; also anti-inflammatory and plaque-stabilizing effects

Uses: Primary and secondary prevention of cardiovascular events, hypercholesterolemia, post-MI (all patients regardless of cholesterol level)

Adverse effects:

Myopathy / rhabdomyolysis (serious - check CK)
Hepatotoxicity (elevated liver enzymes)
GI disturbances
Risk ↑ with co-administration of fibrates or CYP3A4 inhibitors

Q7. Classify Drugs in Cardiac Arrhythmias; Pharmacological Basis of Nitrates in Angina

Classification of Antiarrhythmic Drugs (Vaughan Williams)

Class	MOA	Example
Class I - Na⁺ channel blockers
Ia	↓ max upstroke, ↑ APD	Quinidine, Procainamide
Ib	↓ APD	Lidocaine, Mexiletine
Ic	Strong ↓ conduction, no APD change	Flecainide, Propafenone
Class II - Beta-blockers	↓ SA/AV node activity	Atenolol, Metoprolol
Class III - K⁺ channel blockers	↑ repolarization/APD	Amiodarone, Sotalol
Class IV - CCBs	↓ SA/AV conduction	Verapamil, Diltiazem
Others		Digoxin, Adenosine

Pharmacological Basis of Nitrates in Angina

Nitrates relieve angina by:

Venodilation (↓ preload) → ↓ ventricular filling pressure → ↓ wall tension → ↓ O₂ demand
Arterial dilation (at higher doses) → ↓ afterload → ↓ O₂ demand
Coronary vasodilation → ↑ blood flow to ischemic areas, especially subendocardium
Dilation of coronary collaterals → ↑ O₂ supply
Specifically relieve coronary spasm in variant/Prinzmetal's angina

Q8. Drugs in Management of MI; Difference in MOA of Enalapril, Amlodipine, and Propranolol

Drugs in MI Management

(See Short Note b above)

Difference in MOA

Drug	Class	Mechanism
Enalapril	ACE Inhibitor	Blocks ACE enzyme → ↓ Angiotensin II → ↓ vasoconstriction + ↓ aldosterone → ↓ BP and cardiac workload. Reduces post-MI remodeling
Amlodipine	Dihydropyridine CCB	Blocks L-type Ca²⁺ channels in vascular smooth muscle → vasodilation → ↓ afterload → ↓ BP. Minimal cardiac rate effect
Propranolol	Non-selective Beta-blocker (β₁ + β₂)	Blocks β₁ receptors in heart → ↓ HR + ↓ contractility → ↓ cardiac O₂ demand; Blocks β₂ → ↓ renin release → ↓ BP

In MI, all three serve different but complementary roles: Enalapril prevents remodeling and mortality, Amlodipine reduces angina by vasodilation, and Propranolol (or selective β-blockers like metoprolol) reduces infarct size and prevents sudden death by limiting sympathetic stimulation.

Sources: Katzung's Basic and Clinical Pharmacology 16th Ed.; Lippincott Illustrated Reviews Pharmacology; Goodman & Gilman's Pharmacological Basis of Therapeutics; The Washington Manual of Medical Therapeutics

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